The immediate objective of this investigation is to develop methods to measure the amount of lung tissue (V sub T) and lung water in contact with the airways. These methods will be based upon the simultaneous differential disappearance rates of insoluble gases, soluble gases, and CO2 labelled with oxygen of mass 18 during rebreathing. These methods will be non-invasive and permit frequent repetition. Measurements will be able to be performed in humans in the healthy state, in acute respiratory distress, and with minor modifications in the unconscious state. Animals will be able to be studied if the trachea is intubated. Factors such as lung volume, dead space, breathing frequency, and cardiac output will be varied in order to determine the most accurate way to use these methods. A variety of analytical systems will be evaluated to develop the simplest and most reliable technique for performing the measurements. Limitations of these new methods for measuring V sub T will be examined by making comparisons with established methods such as ratio of wet to dry weight of the lung, determinations of the pulmonary extravascular water volume (PEV) by the double indicator dilution method, and microscopic assessment of abnormalities of lung tissue. Once the accuracy and limitations of these methods are established, normal values for humans and dogs will be established. Measurements of lung tissue and lung water volume will be made in various disease states suspected of increasing or decreasing these volumes. Clinical applications will include detection, assessment, and observation of response to therapy in the following conditions: diseases with alterations of serum oncotic pressure, diseases with elevated pulmonary vascular pressures, cardiac and non-cardiac pulmonary edema, acute respiratory distress syndrome, "fluid overload syndrome", and interstitial diseases such as sarcoidosis, pulmonary fibrosis, and allergic pneumonias.